Abatacept as salvage therapy in chronic graft-versus-host disease\u2014a retrospective analysis

Tobias Wertheimer,Marius Dohse,Daniel Wolff,Andreas Neubauer,Anna-Sophia Kattner,Matthias Edinger,Daniela Weber,Barbara Holler,Wolfgang Herr,Stephan Mielke,Per Ljungman,Ernst Holler,Gabriel Afram,Martin Heidenreich,Antonio Pérez Martínez,Matthias Fante

doi:10.1007/s00277-021-04434-x

Abstract

The immunomodulatory fusion protein abatacept has recently been investigated for the treatment of steroid-refractory chronic graft-versus-host disease (cGvHD) in a phase 1 clinical trial. We analyzed the safety and efficacy of abatacept for cGvHD therapy in a retrospective study with 15 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and received abatacept for cGvHD with a median age of 49 years. Grading was performed as part of the clinical routine according to the National Institute of Health’s (NIH) consensus criteria at initiation of abatacept and 1, 3, 6, 9 and 12 months thereafter. The median time of follow-up was 191 days (range 55–393 days). Best overall response rate (ORR) was 40%. In particular, patients with bronchiolitis obliterans syndrome showed significant clinical improvement and durable responses following abatacept treatment with a response rate of 89% based on improvement in lung severity score (n = 6) or stabilized lung function (n = 4) or both (n = 3). Infectious complications CTCAE °III or higher were observed in 3/15 patients. None of the patients relapsed from the underlying malignancy. Thus, abatacept appears to be a promising treatment option for cGvHD, in particular for patients with lung involvement. However, further evaluation within a phase 2 clinical trial is required.

Highlights

IntroductionCorticosteroids represent the backbone of cGVHD treatment, but contribute to an already high morbidity and mortality by causing complications such as osteoporosis, myopathy, avascular necrosis, and glaucoma [3, 6]
While allogeneic hematopoietic stem cell transplantation is a well-established, potentially curative therapyMatthias Fante and Daniel Wolff contributed to this work.Corticosteroids represent the backbone of cGVHD treatment, but contribute to an already high morbidity and mortality by causing complications such as osteoporosis, myopathy, avascular necrosis, and glaucoma [3, 6]
The diagnoses leading to allo-HSCT were myeloid disorders (acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), myeloproliferative neoplasia (MPN)) in 10 patients, lymphatic malignancies (acute lymphoblastic leukemia (ALL), and Hodgkin lymphoma (HL)) in four patients and one patient suffering from cytotoxic T lymphocyte-associated protein 4 (CTLA-4) haploinsufficiency

Summary

Introduction

Corticosteroids represent the backbone of cGVHD treatment, but contribute to an already high morbidity and mortality by causing complications such as osteoporosis, myopathy, avascular necrosis, and glaucoma [3, 6]. A substantial number of patients does not respond to corticosteroids alone and require second-line therapy with the recently FDA-approved Bruton’s tyrosine kinase inhibitor ibrutinib or extracorporeal photopheresis [5, 7–9]. First in class immunomodulatory drug exerting its effect by costimulatory blockade and is applied for the treatment of rheumatoid arthritis and other rheumatological diseases [15–17].

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Conclusion